Bacterial cell culture processes have been developed for the growth of single cell bacteria, yeast and molds which can be characterized as encased with a tough cell wall. Mammalian cell culture, however, is much more complex because such cells are more delicate and have a more complex nutrient requirement for development. Large scale culture of bacterial type cells is highly developed and such culture techniques are less demanding and are not as difficult to cultivate as mammalian cells. Bacterial cells can be grown in large volumes of liquid medium and can be vigorously agitated without any significant damage. Mammalian cells, on the other hand, cannot withstand excessive turbulent action without damage to the cells and must be provided with a complex nutrient medium to support growth.
In addition, mammalian cells can have a special requirement because most animal cells must attach themselves to some surface in order to duplicate. On a small scale, mammalian cells have been grown in containers with small wells or pores to provide surface anchors for the cells. However, the cell culture for mammalian cells in a container with microwells generally does not provide sufficient surface area to grow mammalian cells on a large scale basis. Also horizontal roller bottles which are partially filled with nutrient media and in which cells either attach or distributed through the media are used for cell culture. However they are inefficient from a volume perspective and induce shear inhibiting three dimensional growth of delicate tissue. To provide greater surface areas, microcarrier beads have been developed for providing surface areas for the cultured cells to attach. However, microcarrier beads with attached culture cells require means for suspension in a bio-reactor vessel to provide suspension of the cells and fresh nutrients. To obtain suspension, such bio-reactor vessels have used internal propellers or movable mechanical agitation devices which are motor driven so that the moving parts within a vessel cause agitation in the fluid medium for the suspension of mammalian cells carried on microcarrier beads.
Small bio-reactor vessels with internal moving parts may damage mammalian cells and also subject the cells to high fluid shearing stresses. If the microcarrier beads collide with one other in the suspension, the attached culture cells can be damaged.
In summary, bio-reactors used to culture mammalian cells typically utilize mechanical parts, air or fluid movement as a lift mechanism to achieve particle suspension. Such mechanisms induce damage to growing cells or tissues either directly or indirectly by fluid shear.